Clopidogrel Bisulfate Plavix

Structural Formula

HjCO

Ball-and-Stick Model

Structural Formula

HjCO

= Carbon = Hydrogen = Oxygen

= Sulfur

= Chlorine

Nitrogen

= Sulfur

Year of discovery: 1990; Year of introduction: 1997 (Sanofi Aventis/Bristol-Myers Squibb); Drug category: Antiplatelet agent — a substance that prevents the formation of blood clots; Main uses: reduction of thrombotic events for persons with recent stroke, myocardial infarction or established peripheral artery disease. Approximate number of individuals treated since its introduction: Over 20 million; Related drugs: Acetylsalicylic acid (Aspirin).

Blood clots cause about 90% of heart attacks and 80% of strokes. Therefore, substances that are capable of preventing platelets from sticking together can be life-saving. Low-dose acetylsalicylic acid - aspirin - (see page 38) is currently used to decrease the risk of heart attack and occlusive stroke by inhibiting the biosynthesis of thromboxane, a type of prostaglandin that promotes clotting (see below).

Arachidonic Acid

Enzymes

Enzymes

Thromboxane (TXA2)

Thromboxane (TXA2)

The use of aspirin for extended periods carries a small risk of stomach irritation or ulceration even at low doses. The development of Clopidogrel was motivated by the need for a safer medicine for aspirin intolerant people.1

The Sanofi company (now Sanofi Aventis) identified Clopidogrel bisulfate as a very potent oral antiplatelet agent and introduced it in 1997 under the trade name Plavix. It works by a different biochemical mechanism than aspirin.2 Clopidogrel bisulfate inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of glycoprotein GPIIb/llla, a proclotting complex, with high selectivity. This modification of the platelet ADP receptor is irreversible, and the platelets that are exposed to clopidogrel are affected for their remaining lifespan (about 2 weeks), thus inhibiting platelet aggregation.

An earlier product by Sanofi/Roche with the same ring system as clopidogrel, ticlopidine, was found to have similar antiplatelet activity but to be toxic to white blood cells (see structure below). Clopidogrel is not the biologically active agent (it is a prodrug) as it must undergo certain biotransformations to become active. To date the active metabolite has not been identified/

Ticlopidine

Ticlopidine

Recently, the FDA has approved the use of clopidogrel for individuals who have suffered a common form of heart attack in which a sudden blockage of the coronary artery occurs, a condition affecting an estimated 500,000 Americans each year. It has been shown that treatment with clopidogrel after a heart attack improves blood flow in the damaged coronary artery and reduces the risk of new heart attack. Clopidogrel is also used to reduce the risk of stroke. Annual sales of clopidogrel have exceeded three billion dollars.

1, Future Cardiol. 2006, 2, 343-366; 2. Exp. Opin. Pharmacother 2006, 7, 1109-1120; 3. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 11069-11074, Refs. p. 84

PART II. CARDIOVASCULAR AGENTS

0 0

Post a comment